Mesenchymal stem cell-loaded thermosensitive hydroxypropyl chitin hydrogel combined with a three-dimensional-printed poly(ε-caprolactone)/nano-hydroxyapatite scaffold to repair bone defects via osteogenesis, angiogenesis and immunomodulation
Mesenchymal stem cell-loaded thermosensitive hydroxypropyl chitin hydrogel combined with a three-dimensional-printed poly(ε-caprolactone)/nano-hydroxyapatite scaffold to repair bone defects via osteogenesis, angiogenesis and immunomodulation
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间充质干细胞负载热敏羟丙基甲壳素水凝胶与三维打印聚（ε-己内酯）/纳米羟基磷灰石支架相结合，通过成骨、血管生成和免疫调节修复骨缺损
DOI：
10.7150/thno.39167
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发表时间：
2020-01-01
期刊：
影响因子：
12.4
通讯作者：
Xiao, Jun
中科院分区：
文献类型：
--
作者：
Ji, Xiongfa;Yuan, Xi;Xiao, Jun
甲壳素衍生水凝胶因其高度的细胞相容性而被广泛用于骨再生，但其较差的力学性能和对材料与宿主细胞相互作用的了解限制了其实际应用。方法：为了评价新合成的温敏性羟丙基甲壳素水凝胶(HPCH)的骨诱导活性，并提高其力学性能，将包裹了HPCH的间充质干细胞(MSC)注入三维打印的聚己内酯(PCL)/纳米羟基磷灰石(NHA)支架中，形成杂化支架。对支架的力学性能和细胞相容性进行了测试。结果：复合支架具有较好的力学性能和较高的细胞存活率。将MSCs包埋于HPCH中，可通过软骨内成骨适当促进成骨。共培养实验表明，杂化支架促进巨噬细胞分泌生长因子，从而促进血管形成和成骨。Transwell培养证实MSCs对HPCH的炎症反应有调节作用。此外，MSC包裹的HPCH皮下植入证实了M2的激活。结论：PCL/nHA+HPCH杂化支架通过促进成骨和免疫调节有效地促进了血管生成和成骨诱导，在骨再生方面具有良好的应用前景。
Chitin-derived hydrogels are commonly used in bone regeneration because of their high cell compatibility; however, their poor mechanical properties and little knowledge of the interaction between the materials and host cells have limited their practical application.Methods: To evaluate osteoinductivity and enhance the mechanical properties of a newly synthesized thermosensitive hydroxypropyl chitin hydrogel (HPCH), a mesenchymal stem cell (MSC)-encapsulated HPCH was infused into a three-dimensional-printed poly (epsilon-caprolactone) (PCL)/nano-hydroxyapatite (nHA) scaffold to form a hybrid scaffold. The mechanical properties and cell compatibility of the scaffold were tested. The interaction between macrophages and scaffold for angiogenesis and osteogenesis were explored in vitro and in vivo.Results: The hybrid scaffold showed improved mechanical properties and high cell viability. When MSCs were encapsulated in HPCH, osteo-differentiation was promoted properly via endochondral ossification. The co-culture experiments showed that the hybrid scaffold facilitated growth factor secretion from macrophages, thus promoting vascularization and osteoinduction. The Transwell culture proved that MSCs modulated the inflammatory response of HPCH. Additionally, subcutaneous implantation of MSC-encapsulated HPCH confirmed M2 activation. In situ evaluation of calvarial defects confirmed that the repair was optimal in the MSC-loaded HPCH + PCL/nHA group.Conclusions: PCL/nHA + HPCH hybrid scaffolds effectively promoted vascularization and osteoinduction via osteogenesis promotion and immunomodulation, which suggests promising applications for bone regeneration.